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Mitotic errors in somatic cells cause trisomy 21 in about 4.5% of cases and are not associated with advanced maternal age

Abstract

The study of DNA polymorphisms has permitted the determination of the parental and meiotic origin of the supernumerary chromosome 21 in families with free trisomy 21. Chromosomal segregation errors in somatic cells during mitosis were recognized after analysis of DNA markers in the pericentromeric region and (in order to identify recombination events) along the long arm of chromosome 21. Mitotic errors accounted for about 4.5% (11 of 238) of free trisomy 21 cases examined. The mean maternal age of mitotic errors was 28.5 years and there was no association with advanced maternal age.There was no preference in the parental origin of the duplicated chromosome 21. The 43 maternal meiosis II errors in this study had a mean maternal age of 34.1 years — the highest mean maternal age of all categories of chromosomal segregation errors.

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References

  1. Lejeune, J., Gautier, M. & Turpin, R. Etudes des chromosomes somatiques de neuf enfants mongoliens. C. R. Aca. Sci. Paris 248, 1721–1722 (1959).

    CAS  Google Scholar 

  2. Hook, E.B. In Trisomy 21: Research perspectives (eds deLa Cruz F.F. & Gerald P.S.) 11–88 (University Park Press, Baltimore, 1981).

    Google Scholar 

  3. Penrose, L.S. The relative effects of paternal and maternal age in mongolism. J. Genet. 44, 17–28 (1933).

    Google Scholar 

  4. Hassold, T. & Chiu, D. Maternal age-specific rates of numerical chromosomal abnormalities with special reference to trisomy. Hum. Genet. 70, 11–17 (1985).

    Article  CAS  Google Scholar 

  5. Hassold, T.J. & Jacobs, P.A. Trisomy in man. Ann. Rev. Genet. 18, 69–97 (1984).

    Article  CAS  Google Scholar 

  6. Dagna-Bricarelli, F. et al. Parental age and the origin of trisomy 21: a study of 302 families. Hum. Genet. 82, 20–26 (1989).

    Article  CAS  Google Scholar 

  7. Arnheim, N. et al. Molecular evidence for genetic exchanges among ribosomal genes on nonhomologous chromosomes in man and apes. Proc. natn. Acad. Sci. U.S.A. 77, 7373–7327 (1980).

    Article  Google Scholar 

  8. Carothers, A.D. Down syndrome and maternal age: the effect of erroneous assignment of parental origin. Am. J. hum. Genet. 40, 639–645 (1987).

    Google Scholar 

  9. Petersen, M.B. et al. Comparative study of microsatellite and cytogenetic markers for detecting the origin of nondisjoined chromosome 21 in Down syndrome. Am. J. hum. Genet. (in the press).

  10. Antonarakis, S.E. & the Down Syndrome Collaborative Group. Parental origin of the extra chromosome in trisomy 21 as indicated by analysis of DMA polymorphisms. New Engl. J. Med. 324, 872–876 (1991).

    Article  CAS  Google Scholar 

  11. Sherman, S.L. et al. Trisomy 21: association between reduced recombination and nondisjunction. Am. J. hum. Genet. 49, 608–620 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Antonarakis, S.E. et al. The meiotic stage of nondisjunction in trisomy 21: Determination by using DNA polymorphisms. Am. J. hum. Genet. 50, 544–550 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Tanzi, R.E. et al. A genetic linkage map of human chromosome 21: analysis of recombination as a function of sex and age. Am. J. hum. Genet. 50, 551–558 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Warburton, D. Molecular and Cytogenetic studies of Nondisjunction (eds Hassold, T.J. & Epstein, C.J.). Prog. clin. biol. Res. 311, 165–181 (1989).

    Google Scholar 

  15. Warren, A.C. et al. D21S215 is a (GT)n polymorphic marker close to the centromeric alphoid sequences on chromosome 21. Genomics (in the press).

  16. Roeder, G.S. & Stewart, S.E. Mitotic recombination in yeast. Trends Genetics 4, 263–267 (1988).

    Article  CAS  Google Scholar 

  17. Henson, V., Palmer, L., Banks, S., Nadeau, J.H. & Carlson, G.A. Loss of heterozygosity and mitotic linkage maps in the mouse. Proc. natn. Acad. Sci. U.S.A. 88, 6486–6490 (1991).

    Article  CAS  Google Scholar 

  18. Kalousek, D.K. In Molecular and Cytogenetic studies of Nondisjunction (eds Hassold, T.J. & Epstein, C.J.). Prog. clin. biol. Res. 311, 153–163 (1989).

    Google Scholar 

  19. Kunkel, L.M. et al. Analysis of human Y-chromosome -specific reiterated DNA in chromosome variants. Proc. natn. Acad. Sci. U.S.A. 74, 1245–1249 (1977).

    Article  CAS  Google Scholar 

  20. Southern, E.M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  Google Scholar 

  21. Saiki, R. et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230, 1350–1354 (1985).

    Article  CAS  Google Scholar 

  22. Davies, K.E. et al. Use of a chromosome 21 cloned DNA probe for the analysis of nondisjunction in Down syndrome. Hum. Genet. 66, 54–56 (1984).

    Article  CAS  Google Scholar 

  23. Petersen, M.B. et al. Use of short sequence repeat DNA polymorphisms after PCR amplification to detect the parental origin of the additional chromosome 21 in Down syndrome. Am. J. hum. Genet. 48, 65–71 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Cox, D.R. & Shimizu, N. Report of the committee on the genetic constitution of chromosome 21. Human Genome Mapping 11. Cytogenet. Cell Genet. 58, 800–826 (1991).

    Article  Google Scholar 

  25. Warren, A.C. et al. Evidence for reduced recombination on the nondisjoined chromosomes 21 in Down syndrome. Science 237, 652–654 (1987).

    Article  CAS  Google Scholar 

  26. Warren, A.C., Slaugenhaupt, S.A., Lewis, J.G., Chakravarti, A. & Antonarakis, S.E. A genetic linkage map of 17 markers on human chromosome 21. Genomics 4, 579–591 (1989).

    Article  CAS  Google Scholar 

  27. Petersen, M.B. et al. A genetic linkage map of 27 markers on human chromosome 21. Genomics 9, 407–419 (1991).

    Article  CAS  Google Scholar 

  28. Jabs, E.W. et al. Alphoid DNA polymorphisms for chromosome 21 can be distinguished from those of chromosome 13 using probes homologous to both. Genomics 9, 141–146 (1991).

    Article  CAS  Google Scholar 

  29. Burmeister, M. et al. A map of the distal region of the long arm of human chromosome 21 constructed by radiation hybrid mapping and pulsed-field gel electrophoresis. Genomics 9, 19–30 (1991).

    Article  CAS  Google Scholar 

  30. Gardiner, K. et al. Analysis of human chromosome 21: correlation of physical and cytogenetic maps ; gene and CpG island distributions. EMBO J. 9, 25–34 (1990).

    Article  CAS  Google Scholar 

  31. Ichikawa, H. et al. Long-distance restriction mapping of the proximal long arm of human chromosome 21 with Not I linking clones. Proc. natn. Acad. Sci. U.S.A. 89, 23–27 (1992).

    Article  CAS  Google Scholar 

  32. Wang, D., Fang, H., Cantor, C.R. & Smith, C.L. A contiguous Not I restriction map of band q22.3 of human chromosome 21. Proc. natn. Acad. Sci. U.S.A. 89, 3222–3226 (1992).

    Article  CAS  Google Scholar 

  33. Cox, D.R., Burmeister, M., Price, E.R., Kim, S. & Myers, R.M. Radiation hybrid mapping: a somatic cell genetic method for constructing high resolution maps of mammalian chromosomes. Science 250, 245–250 (1990).

    Article  CAS  Google Scholar 

  34. Sharma, V., de Jong, P., Yokobata, K. & Litt, M. Dinucleotide repeat polymorphism at the D21S236 locus. Hum. molec. Genet. 1, 289, (1992).

    PubMed  Google Scholar 

  35. Wernert, A. et al. Dinucleotide repeat polymorphism at the D21S258 locus. Hum. molec. Genet. (in the press).

  36. Van Hul, W. et al. Physical map of the chromosome 21 q region between the centromere and the APP gene. 3rd Intl Workshop on Chromosome 21, Baltimore (1992).

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Antonarakis, S., Avramopoulos, D., Blouin, JL. et al. Mitotic errors in somatic cells cause trisomy 21 in about 4.5% of cases and are not associated with advanced maternal age. Nat Genet 3, 146–150 (1993). https://doi.org/10.1038/ng0293-146

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